Vitamin C intake potentially lowers total cholesterol to improve endothelial function in diabetic patients at increased risk of cardiovascular disease: A systematic review of randomized controlled trials

Background: Vitamin C is one of the most consumed dietary compounds and contains abundant antioxidant properties that could be essential in improving metabolic function. Thus, the current systematic review analyzed evidence on the beneficial effects of vitamin C intake on cardiovascular disease (CVD)-related outcomes in patients with diabetes or metabolic syndrome. Methods: To identify relevant randomized control trials (RCTs), a systematic search was run using prominent search engines like PubMed and Google Scholar, from beginning up to March 2022. The modified Black and Downs checklist was used to assess the quality of evidence. Results: Findings summarized in the current review favor the beneficial effects of vitamin C intake on improving basic metabolic parameters and lowering total cholesterol levels to reduce CVD-risk in subjects with type 2 diabetes or related metabolic diseases. Moreover, vitamin C intake could also reduce the predominant markers of inflammation and oxidative stress like C-reactive protein, interleukin-6, and malondialdehyde. Importantly, these positive outcomes were consistent with improved endothelial function or increased blood flow in these subjects. Predominantly effective doses were 1,000 mg/daily for 4 weeks up to 12 months. The included RCTs presented with the high quality of evidence. Conclusion: Clinical evidence on the beneficial effects of vitamin C intake or its impact on improving prominent markers of inflammation and oxidative stress in patients with diabetes is still limited. Thus, more RCTs are required to solidify these findings, which is essential to better manage diabetic patients at increased risk of developing CVD

Physical exercise potentially targets epicardial adipose tissue to reduce cardiovascular disease risk in patients with metabolic diseases : oxidative stress and inflammation emerge as major therapeutic targets

CITATION: Nyawo, T. A. et al. 2021. Physical exercise potentially targets epicardial adipose tissue to reduce cardiovascular disease risk in patients with metabolic diseases : oxidative stress and inflammation emerge as major therapeutic targets. Antioxidants, 10(11):1758, doi:10.3390/antiox10111758.The original publication is available at https://www.mdpi.comENGLISH ABSTRACT: Excess epicardial adiposity, within a state of obesity and metabolic syndrome, is emerging as an important risk factor for the development of cardiovascular diseases (CVDs). Accordingly, increased epicardial fat thickness (EFT) implicates the exacerbation of pathological mechanisms involving oxidative stress and inflammation within the heart, which may accelerate the development of CVDs. This explains increased interest in targeting EFT reduction to attenuate the detrimental effects of oxidative stress and inflammation within the setting of metabolic syndrome. Here, we critically discuss clinical and preclinical evidence on the impact of physical exercise on EFT in correlation with reduced CVD risk within a setting of metabolic disease. This review also brings a unique perspective on the implications of oxidative stress and inflammation as major pathological consequences that link increased EFT to accelerated CVD risk in conditions of metabolic disease.https://www.mdpi.com/2076-3921/10/11/1758Publisher's versio

Coenzyme Q10 supplementation improves adipokine levels and alleviates inflammation and lipid peroxidation in conditions of metabolic syndrome : a meta-analysis of randomized controlled trials

CITATION: Dludla, P. V., et al. 2020. Q10 Supplementation Improves Adipokine Levels and Alleviates Inflammation and Lipid Peroxidation in Conditions of Metabolic Syndrome: A Meta-Analysis of Randomized Controlled Trials. International Journal of Molecular Sciences. 2020; 21(9). doi:10.3390/ijms21093247The original publication is available at https://www.mdpi.com/journal/ijmsEvidence from randomized controlled trials (RCTs) suggests that coenzyme Q10 (CoQ10) can regulate adipokine levels to impact inflammation and oxidative stress in conditions of metabolic syndrome. Here, prominent electronic databases such as MEDLINE, Cochrane Library, and EMBASE were searched for eligible RCTs reporting on any correlation between adipokine levels and modulation of inflammation and oxidative stress in individuals with metabolic syndrome taking CoQ10. The risk of bias was assessed using the modified Black and Downs checklist, while the Grading of Recommendations Assessment, Development and Evaluation (GRADE) tool was used to evaluate the quality of evidence. Results from the current meta-analysis, involving 318 participants, showed that CoQ10 supplementation in individuals with metabolic syndrome increased adiponectin levels when compared to those on placebo (SMD: 1.44 [95% CI: −0.13, 3.00]; I2 = 96%, p < 0.00001). Moreover, CoQ10 supplementation significantly lowered inflammation markers in individuals with metabolic syndrome in comparison to those on placebo (SMD: −0.31 [95% CI: −0.54, −0.08]; I2 = 51%, p = 0.07). Such benefits with CoQ10 supplementation were related to its ameliorative effects on lipid peroxidation by reducing malondialdehyde levels, concomitant to improving glucose control and liver function. The overall findings suggest that optimal regulation of adipokine function is crucial for the beneficial effects of CoQ10 in improving metabolic health.https://www.mdpi.com/1422-0067/21/9/3247/htmPublishers versio

Expression of Caspase-3 in Circulating Innate Lymphoid Cells Subtypes Is Altered by Treatment with Metformin and Fluvastatin in High-Fat Diet Fed C57BL/6 Mice

The current study aimed to determine the expression levels of caspase-3 in circulating innate lymphoid cell subtypes (ILCs) in a high-fat diet (HFD)-induced prediabetes mouse model. Another critical point was to assess the therapeutic effects of metformin and fluvastatin in modulating caspase-3 activation in ILCs within these HFD-fed mice. Prominent results showed that mice exposed to HFD for 14 weeks displayed impaired glucose tolerance that was accompanied by elevated levels of low-density lipoprotein cholesterol (LDL-c) and altered haematological profile as characterised by significantly increased concentrations of red blood cell count, white cell count and lymphocytes when compared to those fed a low-fat diet (LFD). Moreover, the expression of caspase-3 in ILC1 and ILC3 was significantly increased in the HFD groups in comparison to the LFD-fed group. Notably, six-week treatment with metformin and fluvastatin reduced the caspase-3 activation in ILC subtypes. The reduced caspase-3 activation in ILC1 was inversely associated with HDL-c levels following metformin treatment. Interestingly, the reduced caspase-3 activation in ILC3 was associated with lower total cholesterol following fluvastatin treatment in these HFD-fed mice. However, there were no differences in activation of caspase-3 on ILC2 or any association between caspase-3 activation and changes in body weight or fasting blood glucose. Thus, while HFD-feeding clearly modulates ILCs, potentially leading to pro-apoptotic mechanisms, metformin and fluvastatin may play a major role in protecting against such metabolic disturbances

T cell activation and cardiovascular risk in type 2 diabetes mellitus: a protocol for a systematic review and meta-analysis

Abstract Introduction The burden of non-communicable diseases such as type 2 diabetes mellitus (T2DM) and cardiovascular diseases (CVDs) has drastically increased in developing countries over the years. Although recent evidence points to chronic immune activation to be a significant aspect in the pathogenesis and development of T2DM and CVDs, the exact role of T cells is not fully understood. Therefore, we aim to investigate T cell function and cardio vascular risk in T2DM. In addition, the therapeutic effect of blood glucose-lowering drugs to reverse hyperglycaemia induced T cell dysfunction and myocardial infarction will be reviewed. Methods This will be a systematic review and meta-analysis of published studies assessing T cell activation and cardiovascular risk in adults with T2DM. The search strategy will include medical subject headings (MeSH) words for PubMed/MEDLINE database. The search terms will also be adapted to grey literature, Embase and Cochrane Central Register of Controlled Trials electronic databases. Studies will be independently screened by two reviewers using predefined criteria. Relevant eligible full texts will be screened and data will be extracted. Data extraction will be performed using a pre-piloted structured form. To assess the quality and strengths of evidence across selected studies, the Grading of Recommendations Assessment Development and Evaluation approach will be used. The Cochran’s Q statistic and the I 2 statistics will be used to analyse statistical heterogeneity between studies. If included studies show substantial level of statistical heterogeneity, a random-effects meta-analysis will be performed using R statistical software. Discussions This review will not require ethical approval, and the findings will be disseminated through peer-reviewed publication and conferences. Although other previous studies have reported deregulated T cell function in hyperglycaemia, the underlying mechanisms remain controversial. However, evidence suggests that T cells may be a key component in the development of T2DM and CVDs as its complication. Furthermore, they are a potential diagnostic and therapeutic target in the management of the disease. Systematic review registration PROSPERO CRD4201809974

Uncoupling proteins as a therapeutic target to protect the diabetic heart.

Myocardial remodeling and dysfunction caused by accelerated oxidative damage is a widely reported phenomenon within a diabetic state. Altered myocardial substrate preference appears to be the major cause of enhanced oxidative stress-mediated cell injury within a diabetic heart. During this process, exacerbated free fatty acid flux causes an abnormal increase in mitochondrial membrane potential leading to the overproduction of free radical species and subsequent cell damage. Uncoupling proteins (UCPs) are expressed within the myocardium and can protect against free radical damage by modulating mitochondrial respiration, leading to reduced production of reactive oxygen species. Moreover, transgenic animals lacking UCPs have been shown to be more susceptible to oxidative damage and display reduced cardiac function when compared to wild type animals. This suggests that tight regulation of UCPs is necessary for normal cardiac function and in the prevention of diabetes-induced oxidative damage. This review aims to enhance our understanding of the pathophysiological mechanisms relating to the role of UCPs in a diabetic heart, and further discuss known pharmacological compounds and hormones that can protect a diabetic heart through the modulation of UCPs

Linking LOXL2 to Cardiac Interstitial Fibrosis

International audienceCardiovascular diseases (CVDs) are the leading causes of death worldwide. CVD pathophysiology is often characterized by increased stiffening of the heart muscle due to fibrosis, thus resulting in diminished cardiac function. Fibrosis can be caused by increased oxidative stress and inflammation, which is strongly linked to lifestyle and environmental factors such as diet, smoking, hyperglycemia, and hypertension. These factors can affect gene expression through epigenetic modifications. Lysyl oxidase like 2 (LOXL2) is responsible for collagen and elastin cross-linking in the heart, and its dysregulation has been pathologically associated with increased fibrosis. Additionally, studies have shown that, LOXL2 expression can be regulated by DNA methylation and histone modification. However, there is a paucity of data on LOXL2 regulation and its role in CVD. As such, this review aims to gain insight into the mechanisms by which LOXL2 is regulated in physiological conditions, as well as determine the downstream effectors responsible for CVD development

Huntington's Disease Genetic Heterogeneity In African Patients

SUMMARY Huntington’s disease has been reported to occur rarely in black patients. A new genetic variant “Huntington’s disease like 2” (HDL2), occurring more frequently in Blacks, has recently been described. The absence of an expanded tri-nucleotide repeat at the chromosome 4 HD locus was previously regarded as a way of excluding classical Huntington’s disease (HD). The objective of this paper is to describe a number of black patients with genetically proven Huntington’s disease and review its occurrence in Africa. Methods: Eleven black families (twelve subjects), with genetically proven Huntington’s disease are described, nine from the Dr George Mukhari Hospital and two from private practice in Tshwane. Results: Chorea was present in all 12 patients and cognitive decline in nine. Nine had an age of onset between 30-50 years. Six families exhibited expansion of the trinucleotide repeat at the chromosome 4, IT 15 gene (HD) and five a Junctophilin (JPH3) trinucleotide expansion at chromosome 16 (HDL2). The HDL2 subtype showed a tendency towards a later age of onset. Conclusions: The clinical presentation of the two genotypes (i.e., HD or HDL2) appears to be similar. The actual rate of occurrence of Huntington’s disease in Blacks may require reassessment. With the number of Huntington’s chorea patients occurring in our area (Garankuwa), the possibility of clustering of the condition arises

The effect of underlying inflammation on iron metabolism, cardiovascular risk and renal function in patients with type 2 diabetes

Abstract Aim To investigate the impact of inflammation on iron metabolism, cardiovascular risk and renal function in type 2 diabetes (T2D). Methods A total of 50 patients with T2D were included in this study. The patients were stratified into two groups based on their levels of C‐reactive protein (CRP), namely normal and high levels (n = 25/group). All laboratory tests were measured using standardised methods. Results Fasting plasma glucose levels were elevated in patients with high CRP when compared to those with normal levels (p = 0.0413). Total serum iron levels were lower in patients with high CRP levels (12.78 ± 3.50) when compared to those with normal levels (15.26 ± 4.64), p = 0.0381. However, ferritin and transferrin levels were comparable between the groups (p > 0.05). The mean cell volume (MCV) in the high CRP group was lower (87.66 ± 3.62) than the normal level group (90.79 ± 4.52), p = 0.0096, whilst the lipograms were similar (p > 0.05). The estimated glomerular filtration rate (eGFR) was lower in the high CRP group (98.06 ± 11.64) than the normal level group (104.7 ± 11.11), p = 0.046. Notably, CRP levels were negatively associated with serum iron levels (r = –0.38, p = 0.0061), MCV (r = –0.41, p = 0.0031), potassium (r = –0.37, p = 0.0086) and sodium levels (r = –0.28, p = 0.0471). Regression analyses showed that only CRP (β = –0.16, standard error [SE]: 0.06, p = 0.0125) and sodium (β = 0.51, SE: 0.25, p = 0.0434) levels contributed significantly to the prediction of serum iron levels. Conclusion Underlying inflammation in T2D is associated with increased incidence of hypertension and reduced levels of serum iron, MCV and renal function. Although there was no apparent clinical anaemia or renal dysfunction in these patients, mitigating inflammation may be effective in circumventing the ultimate development of iron deficiency anaemia and chronic kidney disease in T2D

The transcription profile unveils the cardioprotective effect of aspalathin against lipid toxicity in an in Vitro H9c2 model

CITATION: Johnson, R., et al. 2017. The transcription profile unveils the cardioprotective effect of aspalathin against lipid toxicity in an in Vitro H9c2 model. Molecules, 22(2):219, doi:10.3390/molecules22020219.The original publication is available at http://www.mdpi.comAspalathin, a C-glucosyl dihydrochalcone, has previously been shown to protect cardiomyocytes against hyperglycemia-induced shifts in substrate preference and subsequent apoptosis. However, the precise gene regulatory network remains to be elucidated. To unravel the mechanism and provide insight into this supposition, the direct effect of aspalathin in an isolated cell-based system, without the influence of any variables, was tested using an H9c2 cardiomyocyte model. Cardiomyocytes were exposed to high glucose (33 mM) for 48 h before post-treatment with or without aspalathin. Thereafter, RNA was extracted and RT2 PCR Profiler Arrays were used to profile the expression of 336 genes. Results showed that, 57 genes were differentially regulated in the high glucose or high glucose and aspalathin treated groups. Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) analysis revealed lipid metabolism and molecular transport as the biological processes altered after high glucose treatment, followed by inflammation and apoptosis. Aspalathin was able to modulate key regulators associated with lipid metabolism (Adipoq, Apob, CD36, Cpt1, Pparγ, Srebf1/2, Scd1 and Vldlr), insulin resistance (Igf1, Akt1, Pde3 and Map2k1), inflammation (Il3, Il6, Jak2, Lepr, Socs3, and Tnf13) and apoptosis (Bcl2 and Chuk). Collectively, our results suggest that aspalathin could reverse metabolic abnormalities by activating Adipoq while modulating the expression of Pparγ and Srebf1/2, decreasing inflammation via Il6/Jak2 pathway, which together with an observed increased expression of Bcl2 prevents myocardium apoptosis.http://www.mdpi.com/1420-3049/22/2/219Publisher's versio